The extracellular matrix (ECM) provides a critical structural support for cells and tissues. Defects or changes in the extracellular matrix as a result of excessive deposition or accumulation of ECM components can lead to ECM-mediated diseases or conditions. Among these are collagen-mediated diseases or conditions characterized by the presence of abundant fibrous septae of collagen. Often the only approved treatment for such diseases or conditions is surgery, which can be highly invasive. Other treatments, such as needle aponeurotomy for the treatment of Dupuytren's syndrome (also called Dupuytren's contracture) or liposuction for cellulite, also are highly invasive.
Collagenase, an enzyme active at neutral pH that degrades collagen, has been used to treat ECM-mediated conditions such as cellulite (see e.g., published U.S. application serial No. US20070224184); Dupuytren's syndrome (see e.g. U.S. Patent No. USRE 39941; U.S. Pat. Nos. 5,589,171; 6,086,872); and Peyronie's disease (see e.g., U.S. Pat. No. 6,022,539). Collagenase, however, is capable of irreversibly cleaving collagens of type I, II and III. The prolonged activity of collagenase limits the dosages that can be administered and also risks side effects associated with prolonged activation. Hence, there is a need for alternative treatments of ECM-mediated diseases and conditions. Accordingly, it is among the objects herein to provide methods and combinations of activatable matrix-degrading enzymes for the treatment of ECM-mediated diseases and conditions.